The 2200 known serotypes of Salmonella may be grouped into
Typhoid fever is a systemic disease caused by Salmonella typhi. Symptoms are high fever, prostration, abdominal pain, and a rose-colored rash. Diagnosis is clinical and confirmed by culture. Treatment is with ceftriaxone or ciprofloxacin.
About 400 to 500 cases of typhoid fever are reported annually in the US, mainly among US travelers returning from endemic regions. Typhoid bacilli are shed in stool of asymptomatic carriers or in stool or urine of people with active disease. Inadequate hygiene after defecation may spread S. typhi to community food or water supplies. In endemic areas where sanitary measures are generally inadequate, S. typhi is transmitted more frequently by water than by food. In developed countries, transmission is chiefly by food that has been contaminated during preparation by healthy carriers. Flies may spread the organism from feces to food. Occasional transmission by direct contact (fecal-oral route) may occur in children during play and in adults during sexual practices. Rarely, hospital personnel who have not taken adequate enteric precautions have acquired the disease when changing soiled bedclothes.
The organism enters the body via the GI tract and gains access to the bloodstream via the lymphatic channels. Intestinal ulceration, hemorrhage, and perforation may occur in severe cases.
About 3% of untreated patients, referred to as chronic enteric carriers, harbor organisms in their gallbladder and shed them in stool for > 1 yr. Some carriers have no history of clinical illness. Most of the estimated 2000 carriers in the US are elderly women with chronic biliary disease. Obstructive uropathy related to schistosomiasis may predispose certain typhoid patients to urinary carriage. Epidemiologic data indicate that typhoid carriers are more likely than the general population to develop hepatobiliary cancer.
Symptoms and Signs
The incubation period (usually 8 to 14 days) is inversely related to the number of organisms ingested. Onset is usually gradual, with fever, headache, arthralgia, pharyngitis, constipation, anorexia, and abdominal pain and tenderness. Less common symptoms include dysuria, nonproductive cough, and epistaxis.
Without treatment, the temperature rises in steps over 2 to 3 days, remains elevated (usually 39.4 to 40°C) for another 10 to 14 days, begins to fall gradually at the end of the 3rd wk, and reaches normal levels during the 4th wk. Prolonged fever is often accompanied by relative bradycardia and prostration. CNS symptoms such as delirium, stupor, or coma occur in severe cases. In about 10% of patients, discrete pink, blanching lesions (rose spots) appear in crops on the chest and abdomen during the 2nd wk and resolve in 2 to 5 days. Splenomegaly, leukopenia, anemia, liver function abnormalities, proteinuria, and a mild consumption coagulopathy are common. Acute cholecystitis and hepatitis may occur.
Late in the disease, when intestinal lesions are most prominent, florid diarrhea may occur, and the stool may contain blood (occult in 20% of patients, gross in 10%). In about 2% of patients, severe bleeding occurs during the 3rd wk, with a mortality rate of about 25%. An acute abdomen and leukocytosis during the 3rd wk may suggest intestinal perforation, which usually involves the distal ileum and occurs in 1 to 2% of patients.Pneumonia may develop during the 2nd or 3rd wk and may be due to secondary pneumococcal infection, although S. typhi can also cause pulmonary infiltrates. Bacteremia occasionally leads to focal infections such as osteomyelitis, endocarditis, meningitis, soft-tissue abscesses, glomerulitis, or GU tract involvement. Atypical presentations, such as pneumonitis, fever only, or, very rarely, symptoms consistent with UTI, may delay diagnosis. Convalescence may last several months.
In 8 to 10% of untreated patients, symptoms and signs similar to the initial clinical syndrome recur about 2 wk after defervescence. For unclear reasons, antibiotic therapy during the initial illness increases the incidence of febrile relapse to 15 to 20%. If antibiotics are restarted at the time of relapse, the fever abates rapidly, unlike the slow defervescence that occurs during the primary illness. Occasionally, a 2nd relapse occurs.
Other infections causing a similar presentation include other Salmonella infections, the major rickettsioses, leptospirosis, disseminated TB, malaria, brucellosis, tularemia, infectious hepatitis, psittacosis, Yersinia enterocolitica infection, and lymphoma. Early in its clinical course, typhoid fever may resemble malaria.
Cultures of blood, stool, and urine should be obtained. Blood cultures are usually positive only during the first 2 wk of illness, but stool cultures are usually positive during the 3rd to 5th wk. If these cultures are negative and typhoid fever is strongly suspected, culture from a bone marrow biopsy specimen may reveal the organism.
Typhoid bacilli contain antigens (O and H) that stimulate the host to form corresponding antibodies. A 4-fold rise in O and H antibody titers in paired specimens obtained 2 wk apart suggests S. typhi infection. However, this test is only moderately (70%) sensitive and lacks specificity; many nontyphoidal Salmonella strains cross-react, and liver cirrhosis causes false-positives.
Without antibiotics, the mortality rate is about 12%. With prompt therapy, the mortality rate is 1%. Most deaths occur in malnourished people, infants, and the elderly. Stupor, coma, or shock reflects severe disease and a poor prognosis. Complications occur mainly in patients who are untreated or in whom treatment is delayed.
Preferred antibiotics include ceftriaxone 1 g IM or IV q 12 h (25 to 37.5 mg/kg in children) for 14 days and various fluoroquinolones (eg, ciprofloxacin 500 mg po bid for 10 to 14 days, levofloxacin 500 mg po or IV once/day for 14 days, moxifloxacin 400 mg po or IV once/day for 14 days). Chloramphenicol 500 mg po or IV q 6 h is still widely used, but resistance is increasing. Fluoroquinolones may be used in children. Alternative therapies, depending on in vitro sensitivity, include amoxicillin 25 mg/kg po qid, trimethoprim/sulfamethoxazole (TMP/SMX) 320/1600 bid or 10 mg/kg (of the TMP component) bid, and azithromycin 1 g po on day 1, then 500 mg once/day for 6 days.
Corticosteroids may be added to antibiotics to treat severe toxicity. Defervescence and clinical improvement usually follow. Prednisone 20 to 40 mg once/day po (or equivalent) for the first 3 days of treatment usually suffices. Higher doses of corticosteroids (dexamethasone 3 mg/kg IV initially, followed by 1 mg/kg q 6 h for 48 h total), are used in patients with marked delirium, coma, or shock.
Nutrition should be maintained with frequent feedings. While febrile, patients are usually kept on bed rest. Salicylates (which may cause hypothermia and hypotension), as well as laxatives and enemas, should be avoided. Diarrhea may be minimized with a clear liquid diet; parenteral nutrition may be needed temporarily. Fluid and electrolyte therapy and blood replacement may be needed.
Intestinal perforation and associated peritonitis call for surgical intervention and broader gram-negative and anti–Bacteroides fragilis coverage.
Relapses are treated the same as the initial illness, although duration of antibiotic therapy seldom needs to be > 5 days.
Patients must be reported to the local health department and prohibited from handling food until proven free of the organism. Typhoid bacilli may be isolated for as long as 3 to 6 mo after the acute illness in people who do not become carriers. Thereafter, 3 stool cultures at weekly intervals must be negative to exclude a carrier state.
Carriers with normal biliary tracts should be given antibiotics. The cure rate is about 60% with amoxicillin 2 g po tid for 4 wk.
In some carriers with gallbladder disease, eradication has been achieved with TMP/SMX and rifampin. In other cases, cholecystectomy with 1 to 2 days of preoperative antibiotics and 2 to 3 days of postoperative antibiotics is effective.
Drinking water should be purified, sewage should be disposed of effectively, milk should be pasteurized, chronic carriers should avoid handling food, and adequate patient isolation precautions should be implemented. Special attention to enteric precautions is important. Travelers in endemic areas should avoid ingesting raw leafy vegetables, other foods stored or served at room temperature, and untreated water. Unless water is known to be safe, it should be boiled or chlorinated before drinking.
A live-attenuated oral typhoid vaccine is available (Ty21a strain) and is about 70% effective. It is given every other day for a total of 4 doses. Because the vaccine contains living S. typhi organisms, it is contraindicated in patients who are immunosuppressed. In the US, the Ty21a vaccine is not used in children < 6 yr. An alternative is the single-dose, IM VI polysaccharide vaccine, which is 64 to 72% effective and is well tolerated, but it is not used in children < 2 yr.
Nontyphoidal Salmonella Infections
Nontyphoidal salmonellae, mainly Salmonella enteritidis, primarily cause gastroenteritis, bacteremia, and focal infection. Symptoms may be diarrhea, high fever with prostration, or symptoms of focal infection. Diagnosis is by cultures of blood, stool, or site specimens. Treatment, when indicated, is with trimethoprim/sulfamethoxazole or ciprofloxacin, with surgery for abscesses, vascular lesions, and bone and joint infections.
Most nontyphoidal Salmonella infections are caused by S. enteritidis. These infections are common and remain a significant public health problem in the US. Many serotypes of S. enteritidis have been given names and are referred to informally as if they were separate species even though they are not. The most common Salmonella serotypes in the US include S. typhimurium, S. heidelberg, S. newport, S. infantis, S. agona, S. montevideo, and S. saint-paul.
Human disease occurs by direct and indirect contact with numerous species of infected animals, the foodstuffs derived from them, and their excreta. Infected meat, poultry, raw milk, eggs, and egg products are common sources of Salmonella. Other reported sources include infected pet turtles and reptiles, carmine red dye, and contaminated marijuana.
Subtotal gastrectomy, achlorhydria (or ingestion of antacids), sickle cell anemia, splenectomy, louse-borne relapsing fever, malaria, bartonellosis, cirrhosis, leukemia, lymphoma, and HIV infection are all risk factors for Salmonella infection.
Diseases caused by nontyphoidal Salmonella sp
Each Salmonella serotype can cause any or all of the clinical syndromes described below, although given serotypes tend to produce specific syndromes. Enteric fever, for instance, is caused by S. paratyphi types A, B, and C.
An asymptomatic carrier state may also occur. However, carriers do not appear to play a major role in large outbreaks of nontyphoidal gastroenteritis. Persistent shedding of organisms in the stool for ≥ 1 yr occurs in only 0.2 to 0.6% of patients with nontyphoidal Salmonella infections.
Symptoms and Signs
Salmonella infection may manifest as
Gastroenteritis usually starts 12 to 48 h after ingestion of organisms, with nausea and cramping abdominal pain followed by diarrhea, fever, and sometimes vomiting. Usually, the stool is watery but may be a pastelike semisolid. Rarely, mucus or blood is present. The disease is usually mild, lasting 1 to 4 days. Occasionally, a more severe, protracted illness occurs.
Enteric fever in a less severe form than typhoid is characterized by fever, prostration, and septicemia.
Bacteremia is relatively uncommon in patients with gastroenteritis. However, S. choleraesuis, S. typhimurium, and S. heidelberg, among others, can cause a sustained and frequently lethal bacteremic syndrome lasting ≥ 1 wk, with prolonged fever, headache, malaise, and chills but rarely diarrhea. Patients may have recurrent episodes of bacteremia or other invasive infections (eg, septic arthritis) due to Salmonella. Multiple Salmonella infections in a patient without other risk factors should prompt HIV testing.
Focal Salmonella infection can occur with or without sustained bacteremia, causing pain in or referred from the involved organ—the GI tract (liver, gallbladder, appendix), endothelial surfaces (eg, atherosclerotic plaques, ileofemoral or aortic aneurysms, heart valves), pericardium, meninges, lungs, joints, bones, GU tract, or soft tissues. Preexisting solid tumors are occasionally seeded and develop abscesses that may, in turn, become a source of Salmonella bacteremia. S. choleraesuis and S. typhimurium are the most common causes of focal infection.
Diagnosis is by isolating the organism from stool or another infected site. In bacteremic and focal forms, blood cultures are positive, but stool cultures are generally negative. In stool specimens stained with methylene blue, WBCs are often seen, indicating inflammatory colitis.
Gastroenteritis is treated symptomatically with oral or IV fluids (see Gastroenteritis: Treatment). Antibiotics do not hasten resolution, may prolong excretion of the organism, and are unwarranted in uncomplicated cases. However, in elderly nursing home residents, infants, and patients with HIV infection, increased mortality dictates treatment with antibiotics. Antibiotic resistance is more common with nontyphoidal Salmonella than with S. typhi. TMP/SMX 5 mg/kg (of the TMP component) po q 12 h for children and ciprofloxacin 500 mg po q 12 h for adults are acceptable regimens. Nonimmunocompromised patients should be treated for 3 to 5 days; patients with AIDS may require prolonged suppression to prevent relapses. Systemic or focal disease should be treated with antibiotic doses as outlined above for typhoid fever. Sustained bacteremia is generally treated for 4 to 6 wk. Abscesses should be drained surgically. At least 4 wk of antibiotic therapy should follow surgery. Infected aneurysms and heart valves and bone or joint infections usually require surgical intervention and prolonged courses of antibiotics. The prognosis is usually good, unless severe underlying disease is present.
Asymptomatic carriage is usually self-limited, and antibiotic treatment is rarely required. In unusual cases (eg, in food handlers or health care workers), eradication may be attempted with ciprofloxacin 500 mg po q 12 h for 1 mo. Follow-up stool cultures should be obtained in the weeks after drug administration to document elimination of Salmonella.
Preventing contamination of foodstuffs by infected animals and humans is paramount. Preventive measures for travelers discussed in Gram-Negative Bacilli: Prevention also apply to most other enteric infections. Case reporting is essential.
Last full review/revision August 2009 by Burke A. Cunha, MD